1. Field of the Invention
This invention relates generally to ion sensors, and more particularly relates to ion-selective-electrode sensors and for methods for production of sensors having extended useful life.
2. Description of the Related Art
Ion-selective-electrode (ISE) sensors that can measure the activity or concentration of analyte ions and metabolites are useful in the analysis of biological fluids including blood, urine, plasma, saliva, spinal fluid, and serum. Such fluids, particularly urine samples, often contain various substances such as drugs and ionic species which can interfere with the determination of the ions to be determined. A primary requirement of the sensor is that it have a high sensitivity to the analyte of interest so that it can accurately determine the concentration of that analyte. Another important requirement is that the sensor has minimal response to ionic species other than the analyte of interest, a characteristic known as selectivity. For example, ISE sensors that are used to determine sodium ions must have a high sensitivity to sodium and also must have a high selectivity for sodium so that the sensor's signals are not affected by the presence of related ions like potassium or chloride.
Recently, solid state ISE sensors have been developed that have cost and convenience in use advantages over conventional ISE sensors as there is no liquid electrolyte solution interposed between a reference electrode and a sensing electrode used to measure the activity of various analyte ions and metabolites. Solid state sensors use a polymeric membrane incorporating an ion-selective agent or ionophore to complex or otherwise attach to the desired ion and, ideally attach only to the desired ion, to provide the sensor's sensitivity and selectivity. The membrane further includes a solvent for the ionophore so that the complexed ion is mobile within the membrane. The membrane thereby changes its ionic content in response to contact with an ionic species analyte in a fluid. In some sensors, multiple analytes may be measured by providing a common fluid flow in contact with different membranes designed for sensitivity to different analytes. In this mode of use, fluids being analyzed are caused to directly contact the membrane layer repeatedly requiring that the membrane's sensitivity and selectivity in combination with the electrode remain constant during repeated exposure to fluids. Stability of the sensors's selectivity is critical, as failure to maintain constant selectivity during repeated exposure to fluids may result in inaccurate readings or spurious signals. Changes in specificity will adversely limit the uselife of the sensor. Thus a factor limiting the uselife of an ISE sensor is the retention of, or stability of, the membrane's selectivity for the analyte of interest compared to other related substances during repeated exposure of the membrane to a variety of fluids. For example, membranes designed to measure sodium need to have a known response to other ionic species that may be included in calibrator fluids (e.g. calcium or potassium ions). Uselife is defined as the number of hours a sensor may be exposed to a standard test fluid without causing the calibration slope after exposure to deviate from the calibration slope before exposure by more than 10%.
There is general theoretical understanding of the requirements for producing sensitivity and selectivity within an ISE sensor membrane, however, theory has poor predictive value for defining the chemical structure of a membrane required to retain stability of the critical sensitivity and selectivity characteristics during actual use. This situation is exacerbated since any additives incorporated into the membrane to enhance its stability must be carefully chosen so as to not interfere with the polymeric binder, ionophore, solvent and other chemicals that may be included for plasticizing, manufacturability, etc.
It is known to use a certain class of solvents with potassium ISE sensor membrane compositions containing valinomycin to extend its shelf life (U.S. Pat No. 4, 608,149). In this case, a hydrophobic polymer is used as the binder and the selected solvents plasticize the membrane while being substantially nonvolatile. The nonvolatile nature of the solvent provides extended shelf life for the membrane before operation of the sensor. However this does not address extending the uselife of the sensor.
A remaining shortcoming in sodium ISE sensors is the degradation in the membrane's selectivity as a result of repeated exposure to test fluids containing the analyte of interest as well as substances in the sample fluids other than the analyte of interest Thus, there is a need for a simple and inexpensive method to extend the uselife of ISE sensors by lengthening the stability of the membrane's selectivity characteristics.